The research proposed for Phase I funding will expand on preliminary findings at BioWest that demonstrate the feasibility of the displacement mode of chromatography for the production of pharmaceutical grade oligonucleotides. In certain cases, HPLC is the only large-scale process step that yields the purity levels required for human therapeutic use. The displacement mode is performed under conditions similar to conventional HPLC operations, but instead of a gradient in eluent strength the feed components are displaced from the column by a carefully chosen solution containing a component that is more strongly absorbed than any of the feed components. Concentrations and column loadings in this mode of chromatography are typically ten to one hundred fold higher than in elution chromatography, and so displacement more fully exploits the column and equipment capacity. These factors, together with simplified control aspects, make displacement chromatography a promising manufacturing step. In order to make a commercially viable process step, the research planned for Phase I is to develop displacers and operating procedures to demonstrate the purification of oligonucleotides. The motive goal of this research aims at discovering displacers appropriate to purification of oligonucleotide products and transferring the technique from the bench to the manufacturing setting.